Roche Holding Ltd · SIX:RO
Roche — Technical Presentation (2020)
20 slides from Roche's technical presentation, 2020
Slide 1: FIREFISH Part 2: Efficacy and safety of risdiplam (RG7916) in infants with Type 1 SMA
FIREFISH Part 2: Efficacy and safety of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA) Laurent Servais,1–3* Giovanni Baranello,4,5 Riccardo Masson,4 Maria Mazurkiewicz-Bełdzińska,6 Kristy Rose,7 Dmitry Vlodavets,8 Hui Xiong,9 Edmar Zanoteli,10 Muna El-Khairi,11 Sabine Fuerst
Slide 2: Disclosures
Disclosures • LS is a PI of SMA studies for Roche, Biogen, and AveXis; He has attended SAB of Biogen and AveXis and received consultancy fees from Biogen; He serves on the board for Cytokinetics • GB has received speaker and consultancy honoraria from AveXis, Inc., Roche, PTC, and Sarepta Therapeuti
Slide 3: Introduction
Introduction • Type 1 SMA is a severe, progressive neuromuscular disease, with untreated infants failing to achieve major motor milestones and typically dying before 2 years of age1 • Risdiplam (RG7916) is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases t
Slide 4: A multicenter, global, open-label study
A multicenter, global, open-label study 12 Months 24 Months Risdiplam Risdiplam Extension Part 21 N=41 Genetic diagnosis of 5q SMA Primary endpoint: symptomatic Type 1 SMA • proportion of infants sitting without support for 5 seconds at Month 12 (as assessed by the Gross Motor Scale of the BSID-III)
Slide 5: Part 2 baseline characteristics are reflective of infants with symptomatic Type 1 SMA
Part 2 baseline characteristics are reflective of infants with symptomatic Type 1 SMA Risdiplam (N=41) Age at enrollment, months, median (range) 5.3 (2.2–6.9) Gender, n (%) Female 22 (54) Male 19 (46) Age at onset of symptoms, months, median (range) 1.5 (1.0–3.0) Disease duration, months, median (ra
Slide 6: The study met its primary endpoint of the proportion of infants sitting at Month 12
The study met its primary endpoint of the proportion of infants sitting at Month 12 Without treatment, children with Type 1 SMA are never able to sit without support1 29% Sitting without support for at least 5 seconds* 12/41 infants P<0.0001, performance criterion= 5% *As assessed by item 22 of the
Slide 7: Event-free survival time was greatly improved in infants treated with risdiplam compared with natural history
Event-free survival time was greatly improved in infants treated with risdiplam compared with natural history Natural history data (PNCR) for infants 85% (35/41) of infants were event-free† with Type 1 SMA and two SMN2 copies1 at Month 12 in FIREFISH Part 2‡ endpoint-free* survival (%) Proportion ev
Slide 8: Risdiplam treatment resulted in significant gains in motor milestones after 12 months (HINE-2 items)
Risdiplam treatment resulted in significant gains in motor milestones after 12 months (HINE-2 items) Wobbles Maintain upright all the time Head control 32 44 76% Sits with support at hips Props Stable sit Pivots Sitting 17 20 15 10 62% Supports Stands with weight support Standing 17 5 22% Bouncing W
Slide 9: 90% (37/41) of infants achieved an increase of ≥4 points in CHOP-INTEND total score
90% (37/41) of infants achieved an increase of ≥4 points in CHOP-INTEND total score at Month 12* Without treatment, infants with Type 1 SMA show a steady decline in CHOP-INTEND scores over time1 45 40 CHOP-INTEND total score Change from baseline in 35 The median change 30 from baseline was 25 +20 po
Slide 10: CHOP-INTEND total score continued to improve over months
CHOP-INTEND total score continued to improve over 12 months 30 In natural history, children with Type 1 SMA rarely Mean change from baseline in reach a CHOP-INTEND total CHOP-INTEND total score* 25 score of 40 points1 20 56% (23/41) achieved a 15 CHOP-INTEND score ≥40 at Month 12† in 10 FIREFISH Par
Slide 11: Swallowing and feeding ability was maintained by the majority of infants alive at Month 12
Swallowing and feeding ability was maintained by the majority of infants alive at Month 12 Swallowing 100 Infants alive at Month 12 80 (n=38) 60 40 20 0 Data cut-off: 14 Nov 2019. © 2020 F. Hoffmann-La Roche Ltd. All rights reserved. 10
Slide 12: Swallowing and feeding ability was maintained by the majority of infants alive at Month 12
Swallowing and feeding ability was maintained by the majority of infants alive at Month 12 Swallowing 100 Infants alive at Month 12 80 (n=38) 60 95% (n=36) 40 maintained ability to 20 swallow 0 Data cut-off: 14 Nov 2019 © 2020 F. Hoffmann-La Roche Ltd. All rights reserved. 11
Slide 13: Swallowing and feeding ability was maintained by the majority of infants alive at Month 12
Swallowing and feeding ability was maintained by the majority of infants alive at Month 12 Swallowing Feeding 100 100 Infants alive at Infants alive at Month 12 Month 12 (n=38) 80 (n=38) 80 60 60 95% (n=36) 40 maintained 40 ability to 20 swallow 20 0 0 Data cut-off: 14 Nov 2019 © 2020 F. Hoffmann-La
Slide 14: Swallowing and feeding ability was maintained by the majority of infants alive at Month 12
Swallowing and feeding ability was maintained by the majority of infants alive at Month 12 Swallowing Feeding 100 100 Infants alive at Infants alive at Month 12 Month 12 (n=38) 80 (n=38) 80 89% able to feed orally (n=34) 60 60 95% (n=36) 40 maintained 40 ability to 20 swallow 20 0 0 Data cut-off: 14
Slide 15: Swallowing and feeding ability was maintained by the majority of infants alive at Month 12
Swallowing and feeding ability was maintained by the majority of infants alive at Month 12 Swallowing Feeding 100 100 Infants alive at Infants alive at Month 12 Month 12 (n=38) 80 (n=38) 80 89% able to feed orally (n=34) 60 60 95% (n=36) 40 maintained 40 74% able to feed In a natural history ability
Slide 16: Nearly half of all infants (49%, 20/41) did not require hospitalization up to Month 12
Nearly half of all infants (49%, 20/41) did not require hospitalization up to Month 12* 49% In natural history, children with 20 Type 1 SMA experienced between ~4.2 and 7.6 18 hospitalizations every year1,2 16 There were 1.30 14 hospitalizations per Number of infants patient-year in 12 FIREFISH Part
Slide 17: There have been no drug-related AEs leading to withdrawal or treatment discontinuation
There have been no drug-related AEs leading to withdrawal or treatment discontinuation* Risdiplam (n=41) Patients with at least one AE, n (%) 41 (100) Total number of AEs 254 Total number of deaths, n (%) 3 (7) AE with fatal outcome† 3 (7) SAE 24 (59) SAE leading to withdrawal from treatment 0 SAE l
Slide 18: AEs and SAEs were reflective of underlying disease
AEs and SAEs were reflective of underlying disease* Risdiplam (n=41) The rate of serious Upper respiratory tract infection 19 (46) pneumonia in infants Pneumonia 16 (39) with Type 1 SMA (from both Parts 1 and 2 Pyrexia 16 (39) combined) decreased Constipation 8 (20) Most common AEs, ≥4 patients, app
Slide 19: Conclusions from FIREFISH Part 2 at 12 months
Conclusions from FIREFISH Part 2 at 12 months The primary endpoint was met (P<0.0001)* Risdiplam Infants treatment led achieved to a motor 29% significant improvement milestones, such as sitting (12/41) in motor function† and standing§ that would of infants were sitting without support for 5 seconds
Slide 20: Acknowledgments
Acknowledgments Many thanks to all the patients who participate Many thanks intothese studies all the patients and their families, healthcare who participate professionals in support and the these studies and theirgroups of patient families, healthcare throughout the world professionals and the supp